Martin Laetitia, Catherinot Vincent, Labesse Gilles
Atelier de Bio- et Chimie-Informatique Structurale, Centre de Biochimie Structurale, CNRS UMR5048, Montpellier, France.
Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W325-9. doi: 10.1093/nar/gkl211.
KinDOCK is a new web server for the analysis of ATP-binding sites of protein kinases. This characterization is based on the docking of ligands already co-crystallized with other protein kinases. A structural library of protein kinase-ligand complexes has been extracted from the Protein Data Bank (PDB). This library can provide both potential ligands and their putative binding orientation for a given protein kinase. After protein-protein structural superposition, the ligands are transferred from the template complexes to the target protein kinase. The resulting complexes are evaluated using the program SCORE to compute a theoretical affinity. They can be dynamically visualized to allow a rapid mapping of important steric clashes and potential substitutions relevant for specificity and affinity. These characteristics allow a quick characterization of protein kinase active sites including conformation changes potentially required to accommodate particular ligands. Additionally, promising pharmacophores can be identified in the focussed library. These features will help to rationalize or optimize virtual screening (VS) on larger chemical compound libraries. The server and its documentation are freely available at http://abcis.cbs.cnrs.fr/kindock/.
KinDOCK是一个用于分析蛋白激酶ATP结合位点的新型网络服务器。这种特性描述基于与其他蛋白激酶共结晶的配体的对接。已从蛋白质数据库（PDB）中提取了蛋白激酶 - 配体复合物的结构库。该库可为给定的蛋白激酶提供潜在配体及其假定的结合方向。在蛋白质 - 蛋白质结构叠加后，将配体从模板复合物转移到目标蛋白激酶。使用SCORE程序评估所得复合物以计算理论亲和力。可以对其进行动态可视化，以便快速绘制与特异性和亲和力相关的重要空间冲突和潜在取代。这些特性有助于快速表征蛋白激酶活性位点，包括容纳特定配体可能需要的构象变化。此外，可在聚焦库中识别出有前景的药效团。这些功能将有助于在更大的化合物库上合理化或优化虚拟筛选（VS）。该服务器及其文档可在http://abcis.cbs.cnrs.fr/kindock/免费获取。
